Application of 1-(4-chloropyridine)-2-piperazine_Industrial additives

Application background and overview of 1-(4-chloropyridine)-2-piperazine

1-(4-Chloropyridine)-2-piperazine is a pharmaceutical intermediate that can be used to prepare PAR sodium perborate monohydrate containing a trans-cyclohexanamide structure containing a halogenated pyridyl group and other structures. -1 antagonist. Protease Activated Acceptor-1 (PAR-1) is a recently discovered new target of antiplatelet and antithrombotic drugs. Protease-activated receptor 1 is also called thrombin receptor. Thrombin is activated by the coagulation chain and acts on platelets through the PAR-1 receptor to activate platelets, causing platelet aggregation and thus thrombosis and coagulation. Thrombus caused by PAR-1 is rich in platelet components and is the main cause of arterial thrombosis. PAR-1 antagonists can block thrombin from activating platelets, thereby blocking arterial thrombosis and can be used to treat acute coronary artery disease (Acute Coronary Syndrome).

Applications of 1-(4-chloropyridine)-2-piperazine

The method for preparing a PAR-1 antagonist (I-1) with 1-(4-potassium trifluoroborate-chloropyridine)-2-piperazine is as follows:

Into a 100mL round bottom flask, add 1.84g (10mmol) compound II, 1.98g (10mmol) compound III-1 and 20mL dry THF. The resulting mixture is stirred while cooling in an ice water bath, and 2.48g (12mmol) is added. After DCC, stirring was continued at room temperature overnight. TLC showed the reaction was complete.

The reaction mixture was poured into ice water, stirred, extracted with 50 mL The residue was purified by column chromatography to obtain product I-1, a white solid, ESI-MS, m/z=365 ([M+H]⁺).

References

[1] [China invention, China invention authorization] CN201410635589.2 Trans-cyclohexane amide compounds containing halogenated pyridyl group and their uses